Mortality and admission to intensive care units after febrile neutropenia in patients with cancer.

Febrile neutropenia (FN) is a critical complication of chemotherapy associated with increased in-hospital mortality. However, associations with increased mortality and intensive care unit (ICU) admissions during longer follow-up are not established. Patients treated with standard first-line chemotherapy for solid cancers at Rigshospitalet, Denmark in 2010-2016 were included. Incidence rate ratios (IRR) of all-cause, infectious and cardiovascular mortality, and ICU admissions after FN were analyzed by Poisson regression. Risk factors at the time of FN were analyzed in the subpopulation of patients with FN; all-cause mortality was further stratified by the time periods 0-30, 31-365, and 366+ days after FN. We included 9018 patients with gastric (14.4%) and breast (13.1%) cancer being the most common, 51.2% had locally advanced or disseminated disease and the patients had a median Charlson Comorbidity Index score of 0 (interquartile range, 0-0). During follow-up, 845 (9.4%) experienced FN and 4483 (49.7%) died during 18 775 person-years of follow-up. After adjustment, FN was associated with increased risk of all-cause mortality, infectious mortality, and ICU admissions with IRRs of 1.39 (95% CI, 1.24-1.56), 1.94 (95% CI, 1.43-2.62), and 2.28 (95% CI, 1.60-3.24). Among those with FN, having a positive blood culture and low lymphocytes were associated with excess risk of death and ICU admissions (predominantly the first 30 days after FN), while elevated C-reactive protein and low hemoglobin predicted mortality the first year after FN. The risk of death varied according to the time since FN; adjusted IRR per additional risk factor present for the time periods 0-30, 31-365, and 366+ days after FN were 2.00 (95% CI, 1.45-2.75), 1.36 (95% CI, 1.17-1.57), and 1.17 (95% CI, 0.98-1.41). FN was associated with increased mortality and risk of ICU admissions. An objectively identifiable subgroup of patients among those with FN carried this excess risk.

Development and validation of a cycle-specific risk score for febrile neutropenia during chemotherapy cycles 2-6 in patients with solid cancers: The CSR FENCE score.

The absolute risk reduction by prophylaxis in chemotherapy-induced febrile neutropenia (FN) is largest in patients at highest underlying risk. Therefore, reliable predictive models are needed. Here, we develop and validate such a model for risk of FN during chemotherapy cycles 2-6. A prediction score for risk of FN during the first cycle has recently been published. Patients with solid cancers initiating first-line chemotherapy in 2010-2016 were included. Cycle-specific risk factors were assessed by Poisson regression using generalized estimating equations and random split sampling. The derivation cohort included 4,590 patients treated with 15,419 cycles, wherein 326 (2.1%) FN events occurred. Predictors of FN in multivariable analyses were: higher predicted risk of FN in the first cycle, platinum- or taxane-containing therapies, concurrent radiotherapy, treatment in cycle 2 compared to later cycles, previous FN or neutropenia and not receiving granulocyte colony-stimulating factors. Each predictor added between -2 and 8 points to each patient's score (median score 4; interquartile range, 1-6). The incidence rate ratios for developing FN in the intermediate (score 1-4), high (score 5-6) and very high risk groups (score ≥7) were 7.8 (95% CI, 2.4-24.9), 18.6 (95% CI, 5.9-58.8) and 51.7 (95% CI, 16.5-162.3) compared to the low risk group (score ≤0), respectively. The score had good discriminatory ability with a Harrell's C-statistic of 0.78 (95% CI, 0.76-0.80) in the derivation and 0.75 (95% CI, 0.72-0.78) in the validation cohort (patient n = 2,295, cycle n = 7,670). The Cycle-Specific Risk of FEbrile Neutropenia after ChEmotherapy score is the first published method to estimate cycle-specific risk of FN.

Febrile Neutropenia and Long-term Risk of Infection Among Patients Treated With Chemotherapy for Malignant Diseases.

BACKGROUND: Febrile neutropenia (FN) is a common complication to chemotherapy, associated with increased short-term morbidity and mortality. However, the long-term outcomes after FN are poorly elucidated. We examined the long-term risk of infection and mortality rates in cancer patients with and without FN. METHODS: Patients aged >16 years treated with firstline chemotherapy were followed from 180 days after initiating chemotherapy until first infection, a new treatment with chemotherapy, death, or end of follow-up. Risk factors for infections were analyzed by competing risks regression, with death or another treatment with chemotherapy as competing events. Adjusted incidence rate ratios (aIRRs) of infection and death were analyzed using Poisson regression. In analyses of mortality, infection was included as a time-updated variable. RESULTS: We included 7190 patients with a median follow-up (interquartile range) of 0.58 (0.20-1.71) year. A total of 1370 patients had an infection during follow-up. The aIRRs of infection were 1.86 (95% confidence interval [CI], 1.56-2.22) and 2.19 (95% CI, 1.54-3.11) for patients with 1 or >1 episode of FN compared with those without FN. Mortality rate ratios were 7.52 (95% CI, 6.67-8.48) <1 month after, 4.24 (95% CI, 3.80-4.75) 1-3 months after, 2.33 (95% CI, 1.63-3.35) 3-6 months after, and 1.09 (95% CI, 0.93-1.29) >6 months after an infection, compared with the time before infection. CONCLUSIONS: FN during chemotherapy is associated with a long-term increased risk of infection. Mortality rates are substantially increased for 6 months following an infection.

Development and Validation of a Risk Score for Febrile Neutropenia After Chemotherapy in Patients With Cancer: The FENCE Score.

BACKGROUND: Febrile neutropenia (FN) after chemotherapy causes a high burden of morbidity and mortality. We aimed to develop and validate a risk score to predict FN in the first cycle of chemotherapy. METHODS: We included patients with solid cancers and diffuse large B-cell lymphomas at Rigshospitalet, University of Copenhagen, 2010-2016. Predictors of FN were analyzed using Poisson regression and random split-sampling. RESULTS: Among 6294 patients in the derivation cohort, 360 developed FN. Female sex, older age, cancer type, disease stage, low albumin, elevated bilirubin, low creatinine clearance, infection before chemotherapy, and number of and type of chemotherapy drugs predicted FN. Compared with those at low risk (n = 2520, 40.0%), the incidence rate ratio of developing FN was 4.8 (95% confidence interval [CI] = 2.9 to 8.1), 8.7 (95% CI = 5.3 to 14.1) and 24.0 (95% CI = 15.2 to 38.0) in the intermediate (n = 1294, 20.6%), high (n = 1249, 19.8%) and very high (n = 1231, 19.6%) risk groups, respectively, corresponding to a number needed to treat with granulocyte colony-stimulating factors to avoid one FN event in the first cycle of 284, 60, 34 and 14. The discriminatory ability (Harrell's C-statistic = 0.80, 95% CI = 0.78 to 0.82) was similar in the validation cohort (n = 3163) (0.79, 95% CI = 0.75 to 0.82). CONCLUSION: We developed and internally validated a risk score for FN in the first cycle of chemotherapy. The FENCE score is available online and provides good differentiation of risk groups.

Mortality and health-related quality of life in patients surgically treated for spondylodiscitis.

PURPOSE: To assess mortality, disability, and health-related quality of life (HRQL) in patients surgically treated for spondylodiscitis. METHODS: A retrospective longitudinal study was conducted on all patients surgically treated for spondylodiscitis over a 6-year period at a single tertiary spine center. Indications for surgery, pre- and postoperative neurological impairment, comorbidities, and mortality were recorded. A survey was conducted on all eligible patients with the EuroQol 5-dimension (EQ-5D) questionnaire and Oswestry Disability Index (ODI). RESULTS: Sixty-five patients were diagnosed with spondylodiscitis not related to recent spine surgery. One-year mortality rate was 6%. In all, 36% and 27% had pre- and postoperative neurological impairment, respectively, with only one patient experiencing deterioration postoperatively. At final follow-up (median 2 years), mean ODI was 31% (SD = 22) and mean EQ-5D time trade-off score was 0.639 (SD = 0.262); this was significantly lower than that in the normal population ( p < 0.001). Patients with neurological impairment prior to index surgery had lower EQ-5D scores ( p = 0.005) and higher ODI ( p = 0.02) at final follow-up compared with patients without neurological impairment. CONCLUSIONS: Several years after surgery, patients surgically treated for spondylodiscitis have significantly lower HRQL and more disability than the background population. Neurological impairment prior to index surgery predicts adverse outcome in terms of disability and lower HRQL.

Long-term prognosis and causes of death after spondylodiscitis: A Danish nationwide cohort study.

BACKGROUND: Data on long-term prognosis after spondylodiscitis are scarce. The purpose of this study was to determine long-term mortality and the causes of death after spondylodiscitis. METHODS: A nationwide, population-based cohort study using national registries of patients diagnosed with non-post-operative pyogenic spondylodiscitis from 1994-2009, alive 1 year after diagnosis (n = 1505). A comparison cohort from the background population individually matched for sex and age was identified (n = 7525). Kaplan-Meier survival curves were constructed and Poisson regression analyses used to estimate mortality rate ratios (MRR). RESULTS: Three hundred and sixty-five patients (24%) and 1115 individuals from the comparison cohort (15%) died. Unadjusted MRR for spondylodiscitis patients was 1.76 (95% CI = 1.57-1.98) and 1.47 (95% CI = 1.30-1.66) after adjustment for comorbidity. No deaths were observed in 128 patients under the age of 16 years. Siblings of patients did not have increased long-term mortality compared with siblings of the individuals from the comparison cohort. This study observed increased mortality due to infections (MRR = 2.57), neoplasms (MRR = 1.40), endocrine (MRR = 3.72), cardiovascular (MRR = 1.62), respiratory (MRR = 1.71), gastrointestinal (MRR = 3.35), musculoskeletal (MRR = 5.39) and genitourinary diseases (MRR = 3.37), but also due to trauma, poisoning and external causes (MRR = 2.78), alcohol abuse-related diseases (MRR = 5.59) and drug abuse-related diseases (6 vs 0 deaths, MRR not calculable). CONCLUSIONS: Patients diagnosed with spondylodiscitis have increased long-term mortality, mainly due to comorbidities, particularly substance abuse.

Long-term mortality after Staphylococcus aureus spondylodiscitis: a Danish nationwide population-based cohort study.

OBJECTIVES: To determine the long-term mortality and the causes of death after Staphylococcus aureus spondylodiscitis. METHODS: Nationwide, population-based cohort study using national registries of adults diagnosed with non postoperative S. aureus spondylodiscitis from 1994-2009 and alive 1 year after diagnosis (n Z 313). A comparison cohort from the background population individually matched on sex and age was identified (n Z 1565). Kaplan-Meier survival curves were constructed and Poisson regression analyses used to estimate mortality rate ratios (MRR) adjusted for comorbidity. RESULTS: 88 patients (28.1%) and 267 individuals from the population-based comparison cohort (17.1%) died. Un-adjusted MRR for S. aureus spondylodiscitis patients was 1.77 (95% CI, 1.39-2.25) and 1.32 (95% CI, 1.02-1.71) after adjustment for comorbidity. We observed increased mortality due to infectious (MRR 8.57; 95% CI, 2.80-26.20), endocrine (MRR 3.57; 95%CI, 1.01-12.66), cardiovascular (MRR 1.59; 95% CI, 1.02-2.49), gastrointestinal (MRR 3.21; 95% CI, 1.178.84) and alcohol and drug abuse-related (MRR 10.71; 95% CI, 3.23-35.58) diseases. CONCLUSIONS: Patients diagnosed with S. aureus spondylodiscitis have substantially increased long-term mortality, mainly due to comorbidity. To improve survival after S. aureus spondylodiscitis these patients should be screened for comorbidity and substance abuse predisposing to the disease [corrected].

Microbiological and therapeutic challenges in infectious spondylodiscitis: a cohort study of 100 cases, 2006-2011.

BACKGROUND: The microbiological diagnosis of infectious spondylodiscitis is often difficult to establish and the disease requires prolonged antibiotic treatment. We analyzed the medical records of 100 patients admitted for infectious spondylodiscitis from 2006 to 2011 with an emphasis on (1) the diagnostic utility of blood cultures and invasive biopsies in the microbiological diagnosis, (2) clinical features differentiating Staphylococcus aureus infections from those with other aetiologies, and (3) evaluation of the outcome of the antimicrobial therapy. METHODS: A retrospective chart review was performed. RESULTS: Patients were diagnosed a median of 32 days after symptom onset and treated for a median of 91 days; 68% had abscesses, 65% experienced sequelae, and the 1-y crude mortality was 11%. Blood cultures yielded a diagnosis in 67%. Among blood culture-positive cases, no other culture or polymerase chain reaction results yielded further diagnoses. S. aureus infections comprised 58%. These cases compared to those with other aetiologies were younger, more frequently female, had a higher C-reactive protein, and more often had neutrocytosis, bacteraemia, and abscess formation. Presumed side effects mediated a change in treatment 33 times in 23 patients. Four patients experienced relapse. CONCLUSIONS: This contemporary case-series on infectious spondylodiscitis mostly concurs with previous studies. We emphasize the importance of thorough blood culture sampling before more invasive tests are considered. S. aureus infections exhibit, in particular, prominent pyogenic characteristics. Prospective studies evaluating the choice and duration of antimicrobial treatment are needed.

Effect of feedback on delaying deterioration in quality of compressions during 2 minutes of continuous chest compressions: a randomized manikin study investigating performance with and without feedback.

BACKGROUND: Good quality basic life support (BLS) improves outcome following cardiac arrest. As BLS performance deteriorates over time we performed a parallel group, superiority study to investigate the effect of feedback on quality of chest compression with the hypothesis that feedback delays deterioration of quality of compressions. METHODS: Participants attending a national one-day conference on cardiac arrest and CPR in Denmark were randomized to perform single-rescuer BLS with (n = 26) or without verbal and visual feedback (n = 28) on a manikin using a ZOLL AED plus. Data were analyzed using Rescuenet Code Review. Blinding of participants was not possible, but allocation concealment was performed. Primary outcome was the proportion of delivered compressions within target depth compared over a 2-minute period within the groups and between the groups. Secondary outcome was the proportion of delivered compressions within target rate compared over a 2-minute period within the groups and between the groups. Performance variables for 30-second intervals were analyzed and compared. RESULTS: 24 (92%) and 23 (82%) had CPR experience in the group with and without feedback respectively. 14 (54%) were CPR instructors in the feedback group and 18 (64%) in the group without feedback. Data from 26 and 28 participants were analyzed respectively. Although median values for proportion of delivered compressions within target depth were higher in the feedback group (0-30 s: 54.0%; 30-60 s: 88.0%; 60-90 s: 72.6%; 90-120 s: 87.0%), no significant difference was found when compared to without feedback (0-30 s: 19.6%; 30-60 s: 33.1%; 60-90 s: 44.5%; 90-120 s: 32.7%) and no significant deteriorations over time were found within the groups. In the feedback group a significant improvement was found in the proportion of delivered compressions below target depth when the subsequent intervals were compared to the first 30 seconds (0-30 s: 3.9%; 30-60 s: 0.0%; 60-90 s: 0.0%; 90-120 s: 0.0%). Significant differences were not found in secondary outcome and in other performance variables between the groups and over time CONCLUSIONS: Quality of CPR was maintained during 2 minutes of continuous compressions regardless of feedback in a group of trained rescuers.